Batten Disease Clinical Trial
Official title:
A Multicenter, Multinational, Extension Study to Evaluate the Long-Term Efficacy and Safety of BMN 190 in Patients With CLN2 Disease
Verified date | July 2022 |
Source | BioMarin Pharmaceutical |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The Phase 1/2 study (190-201) evaluated the efficacy and safety of a 300 mg dose of BMN 190 administered every other week (qow) to patients with CLN2. The dose and regimen for this study (190-202) are based on the results of the 190-201 study. The rationale for this phase 2 extension study is to provide patients who complete the 190-201 study with the option to continue BMN 190 treatment. The 190-202 study is an open label extension protocol to assess long-term safety and efficacy.
Status | Completed |
Enrollment | 23 |
Est. completion date | December 10, 2020 |
Est. primary completion date | December 10, 2020 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 3 Years to 16 Years |
Eligibility | Inclusion Criteria: - Must have completed 48 weeks in Study 190-201. - Is willing and able to provide written, signed informed consent. Or, in the case of patients under the age of 18 (or other age as defined by regional law or regulation), provide written assent (if required) and have written informed consent, signed by a legally authorized representative, after the nature of the study has been explained, and prior to performance of research-related procedures. - Males and females who are of reproductive age should practice true abstinence, defined as no sexual activity, during the study and for 6 months after the study has been completed (or withdrawal from the study). If sexually active and not practicing true abstinence, males and females of reproductive age must use a highly effective method of contraception while participating in the study. - If female, of childbearing potential, must have a negative pregnancy test at the Screening Visit and be willing to have additional pregnancy tests done during the study. Exclusion Criteria: - Has had a loss of 3 or more points in the combined motor and language components of the Hamburg CLN2 rating scale between Baseline of Study 190-201 and the Study Completion visit in Study 190-201 and would not benefit from enrolling in the study in the Investigator's discretion. - Has a score of 0 points on the combined motor and language components of the Hamburg CLN2 rating scale. - Is pregnant or breastfeeding, at Baseline, or planning to become pregnant (self or partner) at any time during the study. - Has used any investigational product (other than BMN 190 in 190-201), or investigational medical device, within 30 days prior to Baseline; or is required to use any investigational agent prior to completion of all scheduled study assessments. - Has a concurrent disease or condition that would interfere with study participation, or pose a safety risk, as determined by the Investigator. - Has any condition that, in the view of the Investigator, places the patient at high risk of poor treatment compliance or of not completing the study. |
Country | Name | City | State |
---|---|---|---|
Germany | Universitaetsklinikum Hamburg-Eppendorf | Hamburg | |
Italy | Children's Hospital Bambino Gesù,IRCCS | Rome | Piazza |
United Kingdom | Great Ormond Street Childrens Hospital | London | |
United States | Nationwide Children's Hospital | Columbus | Ohio |
Lead Sponsor | Collaborator |
---|---|
BioMarin Pharmaceutical |
United States, Germany, Italy, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Probability of Unreversed 2-point Decline in Motor-language (ML) Score or Score of 0 | Motor and Language are each 0-3 point subscales in which 3 represents best function and 0 represents loss of function. Thus, the 0-6 point ML score was used as the primary mode of evaluation of loss of function.
In 190-201, the primary endpoint was a responder endpoint: unreversed ML 2-point decline or score of 0 at Week 48 compared to the 50% rate expected in natural history using the 1-sample binomial test. For 190-202, the primary endpoint was revised to assess response over the full duration of follow-up. It is not clear, given the variable follow-up much greater than 48 weeks, what response rate is expected in natural history. For this reason, the assessment of the primary endpoint is based on comparing to natural history data and using the Kaplan-Meier method and Cox proportional hazards model with covariate adjustment (i.e., baseline ML score and age as continuous covariates, and genotype [common alleles] and sex as categorical covariates). |
Up to Week 289 | |
Primary | Probability of Unreversed Motor-language (ML) Score of Zero. | Motor and Language are each 0-3 point subscales in which 3 represents best function and 0 represents loss of function. Thus, the 0-6 point ML score was used as the primary mode of evaluation of loss of function.
In 190-201, the primary endpoint was a responder endpoint: unreversed ML 2-point decline or score of 0 at Week 48 compared to the 50% rate expected in natural history using the 1-sample binomial test. For 190-202, the primary endpoint was revised to assess response over the full duration of follow-up. It is not clear, given the variable follow-up much greater than 48 weeks, what response rate is expected in natural history. For this reason, the assessment of the primary endpoint is based on comparing to natural history data and using the Kaplan-Meier method and Cox proportional hazards model with covariate adjustment (baseline ML score, age, genotype [common alleles], and sex). |
Up to Week 289 | |
Secondary | Whole Brain Volume | Percentage change from Baseline to Last Observation: Whole Brain volume | Baseline (Week 1 of BMN 190-201) to Week 289 / Last observation | |
Secondary | Volume of Cerebrospinal Fluid | Percentage Change from Baseline to last observation: Volume of cerebrospinal fluid | Baseline (Week 1 of BMN 190-201) to Week 289 / Last observation | |
Secondary | Volume of Total Cortical Gray Matter | Percentage Change from Baseline to last observation: Volume of total cortical gray matter | Baseline (Week 1 of BMN 190-201) to Week 289 / Last observation | |
Secondary | Total White Matter Volume | Percentage Change from Baseline to last observation: Total white matter volume | Baseline (Week 1 of BMN 190-201) to Week 289 / Last observation | |
Secondary | Whole Brain Apparent Diffusion Coefficient | Change from Baseline to last observation Whole brain apparent diffusion coefficient | Baseline (Week 1 of BMN 190-201) to Week 289 / Last observation |
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